ABSTRACT Over the past few years, progress in the development of ultrawideband transmit-receive systems for ultrasound imaging has enabled new imaging paradigms. One such application, which our group has developed is ?acoustic angiography?, a superharmonic imaging technique which is based on the fact that when excited with a moderate acoustic pressure near their resonance (2-4 MHz; around MI of 0.5-0.7) ultrasound contrast agents produce broadband content which extends well past 15 MHz. The result is that signals from ultrasound contrast agents can be separated from those from tissue with high efficacy, and the resulting images benefit from the high resolution received data. This new imaging technique has enabled the acquisition of images of microvascular structure with unprecedented resolution and signal-to-noise ratio, and created a paradigm shift in how ultrasound might be used pre-clinically and clinically in assessing tumor associated angiogenesis. For clinical translation, we are targeting to improve the specificity of ultrasound to breast malignancies, and furthermore to improve sensitivity to very small lesions using acoustic angiography. In prior studies, our work has shown the use of acoustic angiography to detect micro-tumors with very high sensitivity and specificity based on their microvascular angiogenic signature, rather than relying on difference in tissue properties of the tumor mass itself. Although the presence of this high-frequency energy from microbubbles has been known about for over a decade, it has not been taken advantage of until our recent work because it requires transducers with an extraordinarily wide bandwidth not currently available. Although our prior studies have shown great promise using multi-element multi-frequency piezoelectric transducers, a more natural match for this moderate-pressure high-bandwidth application is the capacitive micromachined ultrasonic transducer (CMUT). The use of CMUTs provides benefits over piezoelectrics such as the ability to perform with a very wide bandwidth as well as the possibility of multi-frequency configurations through their micromachined production process. In our preliminary studies, we have experimentally shown the feasibility of dual-frequency CMUTs for transmitting low frequency excitation and receive high frequency harmonics. We have also demonstrated novel techniques for eliminating the natural harmonic content produced by CMUT transducers, a limitation which was previously thought to hamper the performance of these devices for nonlinear microbubble imaging. In this project, a team of investigators with extensive experience in contrast ultrasound imaging and acoustic angiography (Dayton) and CMUT transducer design and fabrication (Oralkan) continue to work together to achieve new performance levels in CMUT transducers for contrast-enhanced ultrasound imaging, with the intent of developing a new cancer imaging approach using CMUT arrays and microbubble contrast agents.